Arthropodicidal oxadiazine intermediate

ABSTRACT

Provided is a compound of the formula: ##STR1## This compound is an intermediate to and is used for preparing the arthropodicidal oxidiazine Compound II described in the specification.

This is a division of application Ser. No. 08/418,047, filed Apr. 6,1995.

BACKGROUND OF THE INVENTION

The present invention pertains to an intermediate for the preparation ofan arthropodicide. More particularly, the present invention pertains tomethyl5-Chloro-2,3-dihydro-2-hydroxy-1-((((((N-(methoxycarbonyl)-N-((4-(trifiuoromethoxy)phenyl))amino))carbonyl))hydrazono))-1H-indene-2-carboxylate (designatedCompound I) which is an intermediate in the preparation of anarthropodicidal oxadiazine.

Oxadiazines such as those disclosed in WO 9211249 and WO 9319045 areimportant arthropodicidal compounds, and effective preparative methodsare needed. Compound II, depicted below, is a particularly advantageousarthropodicidal oxadiazine. ##STR2##

Accordingly, this invention provides Compound I which is a usefulintermediate for the preparation of II. WO 9319045 describes genericallymethods for preparing various intermediates, including those of a typesimilar to Compound I.

SUMMARY OF THE INVENTION

According to the present invention there is provided Compound I which isdepicted as follows. ##STR3##

According to the present invention there is also provided a process tomake Compound II from Compound I.

DETAILS OF THE INVENTION

The arthropodicidal oxadiazine Compound II can be prepared by reactionof Compound I with an acetal derivative in the presence of a Lewis acid,optionally in the presence of an acid scavenger. The acetal derivative,is a dialkoxyalkane of 3 to 12 carbon atoms, such as dimethoxymethane,diethoxymethane and the like. It is preferably present in the reactionmixture in excess and can also serve as a solvent. In addition, solventssuch as chloroform, dichloroethane, dichloromethane, tetrahydrofuran andthe like can be employed as a co-solvent. The Lewis acid can be borontrifluoride, phosphorous pentoxide, sulfur trioxide and the like, and isusually present in excess. Phosphorous pentoxide and sulfur trioxide arepreferred. Sulfur trioxide may be used in the form of a complex, forexample with dimethylformamide (viz., SO₃.DMF), and usually them is alsopresent an acid scavenger such as an amine complex (e.g., SO₃.Pyridine).A filter aid such as CELITE (diatomaceous earth) can be added to thereactions employing phosphorus pentoxide. The reaction temperature istypically in the range of 0° to 110° C., with a temperature of about 40°to 70° C. being preferred. The reaction is usually complete within a fewhours. The product can be isolated by standard methods such as quenchingwith aqueous base, extraction of the organics, concentration andcrystallization for the sulfur trioxide reactions or alternativelyfiltration, washing with aqueous base, concentration and crystallizationfor the phosphorous pentoxide reactions.

Compound I can be prepared by reacting Compound III and Compound IV(Equation 1) in an inert solvent such as chloroform, dichloromethane,benzene, toluene, dimethoxy ethylene glycol (glyme) and the like in thepresence of an acid scavenger such as triethylamine, aqueous sodiumbicarbonate and the like. Reaction temperatures can be in the range ofabout -10° to 60° C., with about 25° C. being preferred. The reaction isusually complete within a few hours. The product is isolated by standardmethods such as aqueous work up, concentration and crystallization froma suitable solvent. ##STR4##

Compound III can be prepared by reacting methyl5-chloro-2,3-dihydro-2-hydroxy-1-oxo-1H-indene-2-carboxylate withhydrazine monohydrate according to the first part of step B of Example 2in WO 9211249. As described therein, Compound III was isolated as ayellow solid but not named.

Compound IV can be prepared by treating Compound V (Equation 2) withbase such as sodium hydride, sodium methoxide and the like in a solventsuch as benzene, toluene and the like and a co-solvent such as glyme toform the corresponding salt of V, then treating this salt with an excessof phosgene. Reaction temperatures are in the range of about -10° to100° C. with a range of 25° to 60° C. being preferred. The reaction isusually complete in a few hours. ##STR5##

Compound V may be prepared from the compound VI by standard methods. Onesuch method involves reacting Compound VI with methyl chloroformate inthe presence of acid scavenger such as diethylaniline, triethylamine,aqueous potassium carbonate and the like (Equation 3), optionally in asolvent such as diethyl ether, dichloromethane and the like. Reactiontemperatures are typically in the range of about 0° to 100° C. withtemperatures 25° to 70° C. being preferred. The reaction is usuallycomplete within a few hours. ##STR6##

The following Examples serve to illustrate the present invention.

EXAMPLE 1 Preparation of methyl5-chloro-2,3-dihydro-2-hydroxy-1-((((((N-(methoxycarbonyl)-N-((4-(trifluoromethoxy)phenyl))amino))carbonyl))hydrazono))-1H-indene-2-carboxylate(Compound I).

Methyl chloroformate, 5.4 g (0.0571 moles), was added to a mixture of 5g (0.0282 moles) of p-trifluoromethoxyaniline and 10.5 g (0.0704 moles)of N,N-diethylaniline cooled in an ice bath. When the addition wascomplete, the mixture was warmed to 70° C. then allowed to cool toambient temperature and poured into 200 mL of 1N hydrochloric acid. Thismixture was extracted with three 50 mL aliquots of ethyl acetate, andthe combined extracts were washed with 100 mL of 1N hydrochloric acid,dried with MgSO₄, and evaporated to give 5 g of Compound V.

¹ H NMR (CDCl₃, 400 MHz) δ 7.41 (d, 2H), 7.16 (d, 2H), 6.67 (s, 1H),3.78 (s, 3H).

Compound V, 4 g (0.0170 moles), was added to 0.68 g (0.0.170 moles) ofsodium hydride, 40 mL of benzene, and 8 mL of 1,2-dimethoxyethane andthe mixture was gently warmed until gas evolution ceased. The mixturewas allowed to cool to ambient temperature and then diluted with benzeneuntil the mixture, a slurry, was thin enough to transfer. The slurry,was added to 60 mL of a 1.93M solution of phosgene in toluene at 0° to10° C. After the addition, the mixture was allowed to warm to roomtemperature and excess phosgene was removed by the passing nitrogen gasthrough the mixture, whereupon the volume of the mixture was reduced byabout half. Compound IV was present in solution and was reacted, withoutisolation, in the next step.

The above mixture containing IV was added to a mixture of 4.33 g (0.0170mol) of methyl5-chloro-1-hydrazono-2,3-dihydro-2-hydroxy-1H-indene-2-carboxylate(Compound III) and 1.68 g (0.0166M) of triethylamine in 50 mL ofdichloromethane. The combined mixture was stirred at ambient temperaturefor 2 h. This mixture was then poured into 1 L (1N) hydrochloric acidand extracted with three 500 mL aliquots of ethyl acetate. The combinedextracts were dried with MgSO₄ and concentrated to effectcrystallization of the product from solution. The crystals werecollected, washed with ether/hexanes and dried to give 5.22 g ofCompound I, m.p. 168°-168.5° C.

IR (nujol) 3394, 3228, 1753, 1738, 1681, 1641, 1594, 1546, 1524, 1503,1421, 1327, 1241, 1179, 1135, 1087, 1048, 1021, 963, 877, 835 cm⁻¹.

¹ H NMR (400 MHz, CDCl₃) δ 12.54 (s, 1H), 7.80 (d, 1H), 7.30-7.20 (m,6H), 4.41 (s, 1H), 3.79 (s, 3H), 3.76 (s, 3H), 3.50 (1/2ABq, 1H) 3.36(1/2ABq, 1H).

EXAMPLE 2 Illustration of the preparation of arthropodicidal Compound IIfrom Compound I.

Phosphorus pentoxide, 42 g (0.295 mole), was added to a mixture of 60.71g (0.118 moles) of compound I, 60 g of CELITE, 400 mL ofdimethoxymethane, and 400 mL of dichloroethane. The mixture was refluxedfor 4.5 h, then an additional portion of phosphorus pentoxide, 4.4 g(0.0309 mole) of was added and the mixture was refluxed for anadditional 0.5 h. The mixture was filtered through CELITE after whichthe Celite® was washed thoroughly with dichloromethane. The filtrate,comprising the dichoroethane and dichloromethane solutions, was washedwith 1 L of saturated sodium bicarbonate solution, filtered again anddried with magnesium sulfate. The filtrate was concentrated to a volumeof 1800 mL and was washed again with 800 mL of saturated sodiumbicarbonate solution. The organic layer was dried with MgSO₄ andconcentrated to give compound II as a viscous oil which was crystallizedfrom hexanes/diethylether to give 46 g of solid. The spectral propertiesof II were consistent with a compound of this structure.

What is claimed is:
 1. A process for preparing a compound of theformula: ##STR7## which comprises: contacting the compound having theformula: ##STR8## with an acetal derivative in the presence of a Lewisacid.
 2. The process of claim 1 wherein the acetal derivative is adialkoxyalkane having from 3 to 12 carbon atoms.
 3. The process of claim1 wherein the Lewis acid is selected from boron trifluoride, sulfurtrioxide and phosphorous pentoxide.
 4. The process of claim 1 whereinthe acetal derivative is selected from dimethoxymethane anddiethoxyethane and the Lewis acid is phosphorous pentoxide.